Neutrophilic leukocytes participate in acute inflammation by defending host tissue against microbial invasion, but in doing so produce inflammatory changes in host tissues through release of toxic lysosomal and oxidant products. At the site of acute inflammation, activity of the neutrophil is influenced by a variety of extracellular stimuli including microbes, complement components and arachiodonic acid (AA) products from adjacent cells. The ambient glucose concentration, often low at inflammatory sites, also affects neutrophil function in that glucose is the prime substrate for cellular anaerobic glycolysis, a critical metabolic pathway for the mature neutrophil. I propose to study some of these important regulating influences on human neutrophils, the first of which involves the role of AA and its metabolites. The effects of exogenous AA (and its products) generated by adjacent neutrophils or cells such as platelets, monocytes or vascular endothelium will be investigated on in vitro neutrophil adhesiveness, locomotion and microbicidal function. In addition, I will study neutrophil glucose metabolism with emphasis on transmembrane glucose transport and glycogenolysis. Having gained some initial insight into these parameters already, I will explore the effects of both soluble chemotaxins (C5a and nFormyl-Met-Leu-Phe) and AA (and its products) on transmembrane glucose transport and glycogenolysis. I will attempt to correlate changes in these aspects of glucose metabolism with subsequent effects on the cell's function to clarify the neutrophil's mechanism for energy homeostasis in the complex local environment attending inflammation.